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NM_032444.4(SLX4):c.1114C>T (p.Arg372Trp) AND Fanconi anemia

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Apr 17, 2021
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000697617.6

Allele description [Variation Report for NM_032444.4(SLX4):c.1114C>T (p.Arg372Trp)]

NM_032444.4(SLX4):c.1114C>T (p.Arg372Trp)

Gene:
SLX4:SLX4 structure-specific endonuclease subunit [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
16p13.3
Genomic location:
Preferred name:
NM_032444.4(SLX4):c.1114C>T (p.Arg372Trp)
HGVS:
  • NC_000016.10:g.3601028G>A
  • NG_028123.1:g.15557C>T
  • NM_032444.4:c.1114C>TMANE SELECT
  • NP_115820.2:p.Arg372Trp
  • LRG_503t1:c.1114C>T
  • LRG_503:g.15557C>T
  • NC_000016.9:g.3651029G>A
  • NM_032444.2:c.1114C>T
Protein change:
R372W
Links:
dbSNP: rs781393524
NCBI 1000 Genomes Browser:
rs781393524
Molecular consequence:
  • NM_032444.4:c.1114C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Fanconi anemia (FA)
Synonyms:
Fanconi pancytopenia; Fanconi's anemia
Identifiers:
MONDO: MONDO:0019391; MeSH: D005199; MedGen: C0015625; Orphanet: 84; OMIM: PS227650

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000826238Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Apr 17, 2021) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Low prevalence of SLX4 loss-of-function mutations in non-BRCA1/2 breast and/or ovarian cancer families.

de Garibay GR, Díaz A, Gaviña B, Romero A, Garre P, Vega A, Blanco A, Tosar A, Díez O, Pérez-Segura P, Díaz-Rubio E, Caldés T, de la Hoya M.

Eur J Hum Genet. 2013 Aug;21(8):883-6. doi: 10.1038/ejhg.2012.268. Epub 2012 Dec 5.

PubMed [citation]
PMID:
23211700
PMCID:
PMC3722678

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000826238.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been reported to segregate with breast cancer in a family (PMID: 23211700). This variant is present in population databases (rs781393524, ExAC 0.009%). This sequence change replaces arginine with tryptophan at codon 372 of the SLX4 protein (p.Arg372Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 20, 2024